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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #236047

Title: Age-related increases in F344 rat intestine microsomal quercetin glucuronidation

Author
item BOLLING, BRADLEY - TUFTS UNIVERSITY
item COURT, MICHAEL - TUFTS UNIVERSITY
item Blumberg, Jeffrey
item CHEN, C-Y OLIVER - JM USDA HNRCA @ TUFTS

Submitted to: Journal of Federation of American Societies for Experimental Biology
Publication Type: Abstract Only
Publication Acceptance Date: 2/11/2009
Publication Date: 4/18/2009
Citation: Bolling, B.W., Court, M.H., Blumberg, J., Chen, C. 2009. Age-related increases in F344 rat intestine microsomal quercetin glucuronidation. Journal of Federation of American Societies for Experimental Biology. Abstract No. 750.1.

Interpretive Summary:

Technical Abstract: The objective of this study was to establish the extent age modifies intestinal quercetin glucuronidation capacity. Pooled microsomal fractions of three equidistant small intestine (SI) segments from 4, 12, 18, and 28 mo male F344 rats (n=8/group) were employed to model the enzyme kinetics of UDP-glucuronosyltransferase (UGT) activity toward quercetin. Intrinsic clearance (Cint, Vmax/Km) values in the upper, middle and lower SI generally were increased with age. At 18 and 28 mo, Cint values were at least 2-fold larger than 4 mo at 0.0665 mL/min/mg. Within individual activity determinations at 30 and 300 uM quercetin, age-related increases were only significant in the upper and lower SI. In upper SI microsomes at 30 uM quercetin, UGT activity increased 2- and 3-fold at 18 and 28 mo, respectively, from 0.348 nmol/min/mg at 4 mo. Similarly, individual lower SI UGT activity of 12 and 28 mo rats increased nearly 70% from 4 mo (1.44 nmol/min/mg). The lower SI preferentially catalyzed glucuronidation at the 7- position (51% of total metabolites), whereas the upper produced the greatest proportion of 4’- and 3’- conjugates, 26 and 33% respectively. UGT quercetin regioselectivity did not change with age. Therefore, age-related increases in quercetin metabolism depend upon intestinal segment and are more pronounced in the upper and lower sections.